According to a recent study published in Nature, astrocytes, the most abundant glial cells in the brain, require neuronal activity to develop their complex bushy shape. This study reveals that interrupting this developmental process can disrupt brain function.
“Astrocytes play diverse roles that are vital for proper brain function,” says first author Yi-Ting Cheng, a graduate student in Dr. Benjamin Deneen’s lab at Baylor. “For instance, they support the activity of other essential brain cells, neurons; participate in the formation and function of synapses, or neuron-to-neuron connections; release neurotransmitters, chemicals that mediate neuronal communication; and make the blood-brain barrier.”
The researchers discovered that when astrocytes develop, neurons are already present and active, meaning that neurons influence how astrocytes acquire their complex shape. Through several experimental approaches, the team discovered that neurons produce gamma-aminobutyric acid (GABA), which binds to the GABAB receptor on astrocytes. They also found that the regulation of the expression of GABAB receptors in astrocytes does not occur in the same way in different brain regions.
The study suggests that astrocyte development and function involve an intricate pattern of events and proteins triggered by neuronal activity and operate in a region-specific manner. The communication between neurons and glia is crucial in establishing and maintaining higher-order brain function.
The researchers show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. Input from inhibitory neurons functions through astrocytic GABAB receptor, and its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function.
Dr. Benjamin Deneen, who supervised the research, explains, “If astrocytes lose their structure, then synapses do not behave properly and brain function goes awry. Figuring out how astrocytes acquire their complex, bushy structure is essential to understanding how the brain develops and functions and may bring new insight into how neurodevelopmental conditions emerge. In this study, we investigated the cells and processes that direct the development of astrocyte structure.”
These findings offer new insights into how neurons influence astrocyte maturation and provide a deeper understanding of the complex processes underlying brain development and function.